Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene

Raquel Rabionet, Leopoldo Zelante, Núria López-Bigas, Leonardo D'Agruma, Salvatore Melchionda, Gabriella Restagno, Maria Lourdes Arbonés, Paolo Gasparini, Xavier P. Estivill

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Mutations in the GJB2 gene have been identified in many patients with childhood deafness, 35delG being the most common mutation in Caucasoid populations. We have analyzed a total of 576 families/unrelated patients with recessive or sporadic deafness from Italy and Spain, 193 of them being referred as autosomal recessive, and the other 383 as apparently sporadic cases (singletons). Of the 1152 unrelated GJB2 chromosomes analyzed from these patients, 37% had GJB2 mutations. Twenty-three different mutations were detected (1 in-frame deletion, 4 nonsense, 5 frameshift, and 13 missense mutations). Mutation 35delG was the most common, accounting for 82% of all GJB2 deafness alleles. The relative frequency of 35delG in Italy and Spain was different, representing 88% of the alleles in Italian patients and only 55% in the Spanish cases. Eight non-35delG mutations were detected more than once (V37I, E47X, 167deIT, L90P, 312de114, 334delAA, R143W, and R184P), with relative frequencies ranging between 0.5 and 1.6% of the GJB2 deafness alleles. The information based on conservation of amino acid residues, coexistence with a second GJB2 mutation or absence of the mutation in non-deaf control subjects, suggests that most of these missense changes should be responsible for the deafness phenotype.

Original languageEnglish
Pages (from-to)40-44
Number of pages5
JournalHuman Genetics
Volume106
Issue number1
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Deafness
Mutation
Genes
Alleles
Spain
Italy
Connexin 26
Missense Mutation
Chromosomes
Phenotype
Amino Acids
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Rabionet, R., Zelante, L., López-Bigas, N., D'Agruma, L., Melchionda, S., Restagno, G., ... Estivill, X. P. (2000). Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. Human Genetics, 106(1), 40-44. https://doi.org/10.1007/s004390051007

Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. / Rabionet, Raquel; Zelante, Leopoldo; López-Bigas, Núria; D'Agruma, Leonardo; Melchionda, Salvatore; Restagno, Gabriella; Arbonés, Maria Lourdes; Gasparini, Paolo; Estivill, Xavier P.

In: Human Genetics, Vol. 106, No. 1, 2000, p. 40-44.

Research output: Contribution to journalArticle

Rabionet, R, Zelante, L, López-Bigas, N, D'Agruma, L, Melchionda, S, Restagno, G, Arbonés, ML, Gasparini, P & Estivill, XP 2000, 'Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene', Human Genetics, vol. 106, no. 1, pp. 40-44. https://doi.org/10.1007/s004390051007
Rabionet R, Zelante L, López-Bigas N, D'Agruma L, Melchionda S, Restagno G et al. Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. Human Genetics. 2000;106(1):40-44. https://doi.org/10.1007/s004390051007
Rabionet, Raquel ; Zelante, Leopoldo ; López-Bigas, Núria ; D'Agruma, Leonardo ; Melchionda, Salvatore ; Restagno, Gabriella ; Arbonés, Maria Lourdes ; Gasparini, Paolo ; Estivill, Xavier P. / Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. In: Human Genetics. 2000 ; Vol. 106, No. 1. pp. 40-44.
@article{d9250520688e458abe0cc72b3f372421,
title = "Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene",
abstract = "Mutations in the GJB2 gene have been identified in many patients with childhood deafness, 35delG being the most common mutation in Caucasoid populations. We have analyzed a total of 576 families/unrelated patients with recessive or sporadic deafness from Italy and Spain, 193 of them being referred as autosomal recessive, and the other 383 as apparently sporadic cases (singletons). Of the 1152 unrelated GJB2 chromosomes analyzed from these patients, 37{\%} had GJB2 mutations. Twenty-three different mutations were detected (1 in-frame deletion, 4 nonsense, 5 frameshift, and 13 missense mutations). Mutation 35delG was the most common, accounting for 82{\%} of all GJB2 deafness alleles. The relative frequency of 35delG in Italy and Spain was different, representing 88{\%} of the alleles in Italian patients and only 55{\%} in the Spanish cases. Eight non-35delG mutations were detected more than once (V37I, E47X, 167deIT, L90P, 312de114, 334delAA, R143W, and R184P), with relative frequencies ranging between 0.5 and 1.6{\%} of the GJB2 deafness alleles. The information based on conservation of amino acid residues, coexistence with a second GJB2 mutation or absence of the mutation in non-deaf control subjects, suggests that most of these missense changes should be responsible for the deafness phenotype.",
author = "Raquel Rabionet and Leopoldo Zelante and N{\'u}ria L{\'o}pez-Bigas and Leonardo D'Agruma and Salvatore Melchionda and Gabriella Restagno and Arbon{\'e}s, {Maria Lourdes} and Paolo Gasparini and Estivill, {Xavier P.}",
year = "2000",
doi = "10.1007/s004390051007",
language = "English",
volume = "106",
pages = "40--44",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene

AU - Rabionet, Raquel

AU - Zelante, Leopoldo

AU - López-Bigas, Núria

AU - D'Agruma, Leonardo

AU - Melchionda, Salvatore

AU - Restagno, Gabriella

AU - Arbonés, Maria Lourdes

AU - Gasparini, Paolo

AU - Estivill, Xavier P.

PY - 2000

Y1 - 2000

N2 - Mutations in the GJB2 gene have been identified in many patients with childhood deafness, 35delG being the most common mutation in Caucasoid populations. We have analyzed a total of 576 families/unrelated patients with recessive or sporadic deafness from Italy and Spain, 193 of them being referred as autosomal recessive, and the other 383 as apparently sporadic cases (singletons). Of the 1152 unrelated GJB2 chromosomes analyzed from these patients, 37% had GJB2 mutations. Twenty-three different mutations were detected (1 in-frame deletion, 4 nonsense, 5 frameshift, and 13 missense mutations). Mutation 35delG was the most common, accounting for 82% of all GJB2 deafness alleles. The relative frequency of 35delG in Italy and Spain was different, representing 88% of the alleles in Italian patients and only 55% in the Spanish cases. Eight non-35delG mutations were detected more than once (V37I, E47X, 167deIT, L90P, 312de114, 334delAA, R143W, and R184P), with relative frequencies ranging between 0.5 and 1.6% of the GJB2 deafness alleles. The information based on conservation of amino acid residues, coexistence with a second GJB2 mutation or absence of the mutation in non-deaf control subjects, suggests that most of these missense changes should be responsible for the deafness phenotype.

AB - Mutations in the GJB2 gene have been identified in many patients with childhood deafness, 35delG being the most common mutation in Caucasoid populations. We have analyzed a total of 576 families/unrelated patients with recessive or sporadic deafness from Italy and Spain, 193 of them being referred as autosomal recessive, and the other 383 as apparently sporadic cases (singletons). Of the 1152 unrelated GJB2 chromosomes analyzed from these patients, 37% had GJB2 mutations. Twenty-three different mutations were detected (1 in-frame deletion, 4 nonsense, 5 frameshift, and 13 missense mutations). Mutation 35delG was the most common, accounting for 82% of all GJB2 deafness alleles. The relative frequency of 35delG in Italy and Spain was different, representing 88% of the alleles in Italian patients and only 55% in the Spanish cases. Eight non-35delG mutations were detected more than once (V37I, E47X, 167deIT, L90P, 312de114, 334delAA, R143W, and R184P), with relative frequencies ranging between 0.5 and 1.6% of the GJB2 deafness alleles. The information based on conservation of amino acid residues, coexistence with a second GJB2 mutation or absence of the mutation in non-deaf control subjects, suggests that most of these missense changes should be responsible for the deafness phenotype.

UR - http://www.scopus.com/inward/record.url?scp=0034098926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034098926&partnerID=8YFLogxK

U2 - 10.1007/s004390051007

DO - 10.1007/s004390051007

M3 - Article

C2 - 10982180

AN - SCOPUS:0034098926

VL - 106

SP - 40

EP - 44

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 1

ER -